· Bis(diisopropylamino)aluminum Hydride
· (MW 228.36)
(reducing agent useful for regioselective conjugate reduction of enones;1 can hydroaluminate double and triple bonds;2 can reduce carbonyl compounds to alcohols2b)
Solubility: sol THF, ether, hydrocarbons.
Form Supplied in: not commercially available.
Analysis of Reagent Purity: Al-H stretching frequency (1820 cm-1); aluminum content by titration with EDTA and back titration with Zn(OAc)2; hydrogen content by gas evolution analysis.2a,2b
Preparative Methods: easily prepared by the addition of i-Pr2NH to AlH3 (from reaction of 100% H2SO4 with LiAlH4)3 in THF in a 2:1 molar ratio. H2 is evolved during the addition. Reaction is complete after 3 h.3 Highly pure reagent can be made by the reaction of Al metal and i-Pr2NH (1:2 molar ratio) in benzene at 140 °C under 2000 psi H2 pressure.4
Handling, Storage, and Precautions: moisture sensitive.
Regioselective Conjugate Reduction of Enones.
Excellent regioselectivity in the conjugate reduction of some a,b-unsaturated ketones using (i-Pr2N)2AlH has been reported.1 The 1,4-reduction product is formed almost exclusively for ketones of the type R1CH=CR2COR3 (R1 = Me, t-Bu, or Ph; R2 = H or Me; R3 = Me, t-Bu, or Ph) and yields are near quantitative (eq 1). Reactions are typically run in THF at 0 °C (2-4:1 molar ratio hydride:enone) and are complete within 15 min to 1 h. However, the reagent appears to have limited generality. Poor regioselectivities occur in the reductions of methyl vinyl ketone and cyclohexenone. When the enone system is disubstituted at the 4-position
(e.g. Me2C=CHCOMe or isophorone), little or no reaction occurs. On the other hand, cyclopentenone undergoes smooth reduction to give the 1,4-product with only traces of the 1,2-product. Similar extents of regioselectivity are obtainable with HBI2, but this reagent requires elevated temperatures, extended reaction times (9-20 h), a larger excess of hydride (8:1), and gives very poor yields with cyclic ketones.
Hydroalumination of alkynes by (i-Pr2N)2AlH in the presence of a transition metal catalyst (typically 5 mol % Dichlorobis(cyclopentadienyl)titanium) readily takes place to give high yields of the hydrometalated compound.2 This organometallic species can be further functionalized by quenching the alanate with D2O or I2 to give the corresponding deutero or iodo product (eq 2).
The reaction with alkynes is a stereospecific syn addition, giving alkenylaluminum intermediates.2a,c Internal alkynes provide high yields (82-95%) of the cis-alkene. No trace of the trans isomer is observed when the reaction is carried out at 0 °C. A considerable amount of the trans-alkene is formed when the temperature is raised to 25 °C at longer reaction times. Terminal alkynes yield a significant amount of alkane (49-54%) along with the alkene after hydrolysis of the alanate. In the case of unsymmetrical alkynes, regiochemistry is likely determined in the formation of the intermediate alkynyltitanium complex, with the subsequent transmetalation being the slow step of this process (eq 3).2a The transition metal adds preferentially to form the less sterically hindered complex.
Mono- and disubstituted alkenes are hydrometalated in nearly quantitative yields to provide the alkane upon hydrolytic workup. Tri- and tetrasubstituted alkenes give little or no reaction.2c Conjugated dienes react with (i-Pr2N)2AlH (1:2 molar ratio) to give mixtures of 1,2- and 1,4-addition products in fair yields (55-60%). An interesting solvent effect was reported in the reaction of 1,5-hexadiene. In THF an 8:1 mixture of alkane and monoene products is formed in 90% yield, whereas cyclization occurs in benzene to give methylcyclopentane (90%).
Nonenolizable carbonyl compounds are quantitatively reduced to the corresponding alcohols (eq 4).2b Enolizable ketones are reduced in moderate yields (40-45%) employing a 2:1 molar ratio of (i-Pr2N)2AlH to ketone. Stereoselectivity in the reduction of 4-t-butylcyclohexanone decreases when the solvent is changed from THF (92:8 eq:ax alcohols) to benzene (70:30 eq:ax alcohols).
- 1. Ashby, E. C.; Lin, J. J. TL 1976, 3865.
- 2. (a) Ashby, E. C.; Noding, S. R. JOM 1979, 177, 117. (b) Ashby, E. C.; Noding, S. R. JOC 1979, 44, 4364. (c) Ashby, E. C.; Noding, S. R. TL 1977, 4579.
- 3. (a) Ashby, E. C.; Sanders, J. R.; Claudy, P.; Schwartz, R. JACS 1973, 95, 6485. (b) Brown, H. C.; Yoon, H. M. JACS 1966, 88, 1464.
- 4. (a) Ashby, E. C.; Willard, G. F.; Goel, A. B. JOC 1979, 44, 1221. (b) Kovar, R. A.; Ashby, E. C. IC 1971, 10, 893.
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